Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.3.1.21 (
CPT
)
4,580
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Stability of
CPT
free drug and
CPT
-loaded polymeric micelles forming from poly (ethylene glycol)-poly (benzyl aspartate-69) block copolymer in the presence of serum and purified serum albumins were investigated by reverse-phase HPLC and GPC. The hydrolysis of
CPT
and
CPT
-loaded micelles follows pseudo-first-order kinetics. The observed hydrolysis rate constants for
CPT
and
CPT
-loaded micelles were 7.4x10(-3)min(-1) and 0.7x10(-3)h(-1), corresponding to an increase in half-life of
CPT
from 94 min to 990 h, respectively. The half-lives of
CPT
lactone hydrolysis of
CPT
-loaded micelles in the presence of BSA were significantly longer than the control whereas in the presence of
HSA
and serum was shorter than the control, and the similar results were obtained from GPC analyzed for micelles stability. This result suggested that the stability of
CPT
-loaded micelles was significantly decreased only in the presence of human albumin and serum. These were corresponded to the results of
CPT
free drug observed in the presence of albumins or serum. BSA significantly retarded the
CPT
lactone ring opening as compared with the control. On the other hand,
HSA
and serum showed rapid
CPT
lactone ring opening. This was probably due to preferential
HSA
binding to the carboxylate form resulting in a change in the lactone-carboxylate equilibrium, whereas, BSA did not bind to the lactone form, but might promote the self-aggregation of
CPT
and binding to the hydrophobic inner core of the micelles, resulting in enhanced stability of
CPT
-loaded micelles. MSA did not affect the stability of micelles.
...
PMID:Influence of serum and albumins from different species on stability of camptothecin-loaded micelles. 1590 82
The study can be useful for understanding the interaction of camptothecin with human serum albu- min. There are two forms of camptothecin (the carboxylate form (
CPT
-C) and the lactone form (
CPT
-L)) but only the lactone one is pharmacologically active. It was reported earlier that in the presence of
HSA
, the active lactone form of camptothecin changes to inactive carboxylate form and it reduces the antitumor activities of camptothecin. However, those studies were performed at physiological pH (7.4) and with non-oxidized and non-glycosylated albumin. The aim of this study was to investigate the effect of oxidative stress, glycosylation, pH changes and competitor drugs on inactivation of lactone form of camptothecin in albumin solution using measurements of fluorescence anisotropy spectroscopy. It was tried to prove that in vivo camptothecin may be present in higher amount in lactone form than previously thought. Due to a reduction of pH value, a decreased rate of hydrolysis from
CPT
-L to
CPT
-C was observed. It was found in vitro a significant reduction in bound fraction of
CPT
-C to
HSA
oxidized by chloramine T or glycosylated by glucose. Moreover, as a result of block- ing binding of
CPT
-C to
HSA
by competitive compound (flurbiprofen), a decrease in the fluorescence anisotropy of the
HSA
-
CPT
complex was found. This study opens the way to review an application of
CPT
and its derivatives in therapy.
...
PMID:INTERACTION OF CAMPTOTHECIN WITH HUMAN SERUM ALBUMIN DETERMINED BY FLUORESCENCE ANISOTROPY SPECTROSCOPY. 2700 98
